Search for a Shared Genetic or Biochemical Basis for Biofilm Tolerance to Antibiotics across Bacterial Species

Stewart, Philip S.; Williamson, Kerry S.; Boegli, Laura; Hamerly, Timothy; White, Ben; Scott, Liam W.; Hu, Xiao; Mumey, Brendan; Franklin, Michael J.; Bothner, Brian; Vital‐Lopez, Francisco G.; Wallqvist, Anders; James, Garth A.

doi:10.1128/aac.00021-22

Cited by 5 publications

(2 citation statements)

References 113 publications

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“…This suggests that the fundamental mechanisms behind reduced biofilm susceptibility could be similar for different classes of antibiotics and in different organisms, even when it is not possible to identify mutations, mutated genes, or differences in metabolism or gene expression shared between different organisms. As such, data from experimental evolution are in line with the conclusion of a recent study that could not find evidence for a common genetic or biochemical basis for antimicrobial tolerance in biofilms but concluded that many genes, proteins, and metabolic pathways collectively determine the physiological state and susceptibility of bacterial cells in a biofilm 132 .…”

Section: Looking At Biofilm Antimicrobial Susceptibility Through the ...supporting

confidence: 69%

Biofilm antimicrobial susceptibility through an experimental evolutionary lens

Coenye

Bové

Bjarnsholt

2022

npj Biofilms Microbiomes

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Experimental evolution experiments in which bacterial populations are repeatedly exposed to an antimicrobial treatment, and examination of the genotype and phenotype of the resulting evolved bacteria, can help shed light on mechanisms behind reduced susceptibility. In this review we present an overview of why it is important to include biofilms in experimental evolution, which approaches are available to study experimental evolution in biofilms and what experimental evolution has taught us about tolerance and resistance in biofilms. Finally, we present an emerging consensus view on biofilm antimicrobial susceptibility supported by data obtained during experimental evolution studies.

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Section: Looking At Biofilm Antimicrobial Susceptibility Through the ...supporting

confidence: 69%

Biofilm antimicrobial susceptibility through an experimental evolutionary lens

Coenye

Bové

Bjarnsholt

2022

npj Biofilms Microbiomes

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“…One of the hallmarks of chronic P. aeruginosa infections is that they occur in biofilms, where the bacterial cells and their extracellular matrices are bound to a surface, such as host tissue or artificial implant devices [ 14 , 15 ]. As a result, much research has been devoted to characterizing the physiological differences of P. aeruginosa growing in biofilms compared to cells growing in planktonic culture, with an emphasis on identifying factors that make P. aeruginosa biofilms difficult to clear by antibiotics (e.g., [ 16 , 17 , 18 ]). An important factor for bacterial biofilm growth is that the cells are physiologically heterogeneous [ 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

The Pseudomonas aeruginosa RpoH (σ32) Regulon and Its Role in Essential Cellular Functions, Starvation Survival, and Antibiotic Tolerance

Williamson

Dlakić

Akiyama

et al. 2023

IJMS

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The bacterial heat-shock response is regulated by the alternative sigma factor, σ32 (RpoH), which responds to misfolded protein stress and directs the RNA polymerase to the promoters for genes required for protein refolding or degradation. In P. aeruginosa, RpoH is essential for viability under laboratory growth conditions. Here, we used a transcriptomics approach to identify the genes of the RpoH regulon, including RpoH-regulated genes that are essential for P. aeruginosa. We placed the rpoH gene under control of the arabinose-inducible PBAD promoter, then deleted the chromosomal rpoH allele. This allowed transcriptomic analysis of the RpoH (σ32) regulon following a short up-shift in the cellular concentration of RpoH by arabinose addition, in the absence of a sudden change in temperature. The P. aeruginosa ∆rpoH (PBAD-rpoH) strain grew in the absence of arabinose, indicating that some rpoH expression occurred without arabinose induction. When arabinose was added, the rpoH mRNA abundance of P. aeruginosa ∆rpoH (PBAD-rpoH) measured by RT-qPCR increased five-fold within 15 min of arabinose addition. Transcriptome results showed that P. aeruginosa genes required for protein repair or degradation are induced by increased RpoH levels, and that many genes essential for P. aeruginosa growth are induced by RpoH. Other stress response genes induced by RpoH are involved in damaged nucleic acid repair and in amino acid metabolism. Annotation of the hypothetical proteins under RpoH control included proteins that may play a role in antibiotic resistances and in non-ribosomal peptide synthesis. Phenotypic analysis of P. aeruginosa ∆rpoH (PBAD-rpoH) showed that it is impaired in its ability to survive during starvation compared to the wild-type strain. P. aeruginosa ∆rpoH (PBAD-rpoH) also had increased sensitivity to aminoglycoside antibiotics, but not to other classes of antibiotics, whether cultured planktonically or in biofilms. The enhanced aminoglycoside sensitivity of the mutant strain may be due to indirect effects, such as the build-up of toxic misfolded proteins, or to the direct effect of genes, such as aminoglycoside acetyl transferases, that are regulated by RpoH. Overall, the results demonstrate that RpoH regulates genes that are essential for viability of P. aeruginosa, that it protects P. aeruginosa from damage from aminoglycoside antibiotics, and that it is required for survival during nutrient-limiting conditions.

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